Diagnostic imaging allows avoidance of unnecessary invasive surgical interventions by confirmation of the nature of various pathological conditions including differentiating between edema and a tumor, detection of multiple metastases, or detection of mental illness or dementia. Non-invasive imaging may be especially useful for diagnostics of diseases or pathological conditions of the human brain, which is not easily accessible by many conventional probing methods such as biopsy and light imaging. Non-invasive imaging is also needed for diagnosis of Alzheimer disease (AD), the most common form of dementia observed in people over 65 years of age.
The oldest approach to diagnose the AD was demonstration of Alzheimer's plaques in human tissue post mortem by employing small chemical compounds that attached specifically to the plaques and that could be visualized by staining ex vivo or by radioactive scintigram in vivo (Newberg A B et al. 2006 J Nuc Med 47:748).
After mouse models became available for AD and cancers, such as triple negative breast cancer, HER2-positive breast cancer, and glioblastoma, in vivo imaging methods could be developed. In vivo imaging approaches utilized fluorescent agents or tagged antibodies binding specifically to components of the diseased cells or tissues, or employed positron emission tomography (PET; Raymond S B et al. 2008 Plos One 3:e2175, 1; Klunk W E et al. 2004 Annals Neurol 55:306).
Although some of these approaches could demonstrate the existence of the diseased tissues, applications required long exposure times and were of insufficient resolution for clearly distinguishing details, or small Alzheimer's plaques. Breakthrough imaging techniques made use of magnetic resonance imaging (MRI). MRI is one of the most advanced non-invasive imaging systems due to application of high resolution contrast agents that include gadolinium (Gd). However, MRI fails to differentiate pathological conditions occurring within a brain. For example, MRI cannot distinguish cancer types, or even cancer from other malignancies. An inefficiency of many in vivo imaging approaches, including MRI, stems from the inability of the contrasting agents, such as gadolinium, to cross the blood-brain barrier (BBB) in combination with rapid elimination of the contrast agent through the kidneys.